Serum Fibroblast Growth Factor 19 and Total Bile Acid Concentrations Are Potential Biomarkers of Hepatocellular Carcinoma in Patients with Type 2 Diabetes Mellitus

Abstract

Purpose. Type 2 diabetes mellitus (T2DM) carries a high risk of hepatocellular carcinoma (HCC). Both serum fibroblast growth factor 19 (FGF19) and bile acid concentrations are associated with T2DM and HCC. We aimed at evaluating the relationships between FGF19 and bile acid concentrations and HCC in patients with T2DM. Methods. Twenty-seven healthy volunteers (control group), 27 patients with T2DM (T2DM group), 16 patients with newly diagnosed HCC (HCC group), and 10 T2DM patients with newly diagnosed HCC (T2DM-HCC group) were studied at the Affiliated Hospital of Nantong University between June 2016 and June 2017. The serum concentrations of serum FGF19 and total bile acids (TBA) were measured in all the participants. Correlation analysis and multiple stepwise regression analysis of the FGF19 and TBA concentrations were performed in all the participants and in the four groups. Results. The concentrations of FGF19 were 220.5 pg/ml, 185.1 pg/ml, 115.8 pg/ml, and 70.4 pg/ml in the HCC, T2DM-HCC, control, and T2DM groups, respectively (p<0.001), and the TBA concentrations were 21.75 μmol/l, 14.25 μmol/l, 3.6 μmol/l, and 3.1 μmol/l (p<0.001). There were positive correlations between the FGF19 and TBA concentrations across all the participants (r = 0.777; p<0.001), and in the control (r = 0.400; p=0.039), T2DM (r = 0.477; p=0.012), HCC (r = 0.684; p=0.003), and T2DM-HCC (r = 0.673; p=0.033) groups. Conclusions. Simultaneous increase of serum FGF19 and TBA levels may be used as indicators of HCC screening at early stage in patients with T2DM.

Assessment of fibroblast growth factor 19 as a non-invasive serum marker for hepatocellular carcinoma

“…Our results are also consistent with those of Sun et al [ 33 ], who detected higher FGF-19 levels in the HCC and diabetes-HCC groups than in the control and diabetes groups (220.5, 185.1, 115.8, and 70.4 pg/mL, respectively, P < 0.001). All these results indicate that FGF-19 may have a role in the pathogenesis of HCC.…”

“…In line with the results of the current research, Sun et al [ 33 ] detected a positive association between FGF-19 and AFP in HCC patients ( P < 0.05). However, Maeda et al [ 12 ] found no significant association between serum FGF-19 concentrations and AFP.…”

Perilla frutescens Leaf Extract and Fractions: Polyphenol Composition, Antioxidant, Enzymes (α-Glucosidase, Acetylcholinesterase, and Tyrosinase) Inhibitory, Anticancer, and Antidiabetic Activities

“…Recent studies reported that diabetes could contribute to the development of cancer via inflammation, and thus has been identified as a risk factor for cancer and cancer-related mortality [ 36 , 37 ]. Malignant tumors such as hepatocellular carcinoma and breast cancer are important causes of human death, and a significant link between them and diabetes has been evidenced [ 38 , 39 , 40 , 41 ].…”

Gut dysbiosis in nonalcoholic fatty liver disease: pathogenesis, diagnosis, and therapeutic implications

“…On the other hand, the gut microbiota can alter the balance of anti-inflammatory and proinflammatory cytokines secreted by M1 and M2 macrophages by affecting the metabolism of SBAs, thereby affecting the immune function of the liver ( Yang et al., 2021 ). Even small amounts of SBAs produced by the gut microbiota can decrease FXR activity and increase inflammation in the body; however, high amounts of SBAs can produce large amounts of ROS, cause cellular DNA damage, and lead to the development of HCC ( Sun et al., 2020 ). In addition, PBAs can upregulate CXCL16 in hepatic vascular endothelial cells, which in turn leads to the recruitment of NKT cells that can kill tumor cells in a CD1d-dependent manner ( Ma et al., 2018 ).…”